Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB8HCED)

• DOT Name: 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP)
• Synonyms: CNP; CNPase; EC 3.1.4.37
• Gene Name: CNP
• Related Disease: Leukodystrophy, hypomyelinating, 20
• UniProt ID: CN37_HUMAN
• PDB ID: 1WOJ
• EC Number: 3.1.4.37
• Pfam ID: PF13671 ; PF05881
• Sequence:
  MNRGFSRKSHTFLPKIFFRKMSSSGAKDKPELQFPFLQDEDTVATLLECKTLFILRGLPG
  SGKSTLARVIVDKYRDGTKMVSADAYKITPGARGAFSEEYKRLDEDLAAYCRRRDIRILV
  LDDTNHERERLEQLFEMADQYQYQVVLVEPKTAWRLDCAQLKEKNQWQLSADDLKKLKPG
  LEKDFLPLYFGWFLTKKSSETLRKAGQVFLEELGNHKAFKKELRQFVPGDEPREKMDLVT
  YFGKRPPGVLHCTTKFCDYGKAPGAEEYAQQDVLKKSYSKAFTLTISALFVTPKTTGARV
  ELSEQQLQLWPSDVDKLSPTDNLPRGSRAHITLGCAADVEAVQTGLDLLEILRQEKGGSR
  GEEVGELSRGKLYSLGNGRWMLTLAKNMEVRAIFTGYYGKGKPVPTQGSRKGGALQSCTI
  I
• Function: Catalyzes the formation of 2'-nucleotide products from 2',3'-cyclic substrates. May participate in RNA metabolism in the myelinating cell, CNP is the third most abundant protein in central nervous system myelin.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leukodystrophy, hypomyelinating, 20	DISZZRHN	Limited	Unknown	[1]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[14]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[7]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[8]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[8]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[9]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP).	[16]

References

• [1] CNP deficiency causes severe hypomyelinating leukodystrophy in humans. Hum Genet. 2020 May;139(5):615-622. doi: 10.1007/s00439-020-02144-4. Epub 2020 Mar 3.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [9] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [10] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.